Ketamine vs MDMA: Difference to Ketamine and MDMA Therapy

February 15, 2023

Nue Life

Nue Life
This article was medically reviewed by Kristen Davis, PA-C.

Top Points:

  • MDMA works to increase serotonin and oxytocin, while ketamine has dissociative effects caused by a surge of glutamate, the brain’s most abundant excitatory neurotransmitter.
  • Research into the medicinal usage of psychedelics has grown in recent years.
  • Ketamine is available in several forms, and is approved as treatment for depression, anxiety, PTSD, and Bipolar Disorder.

The medical community’s interest in the therapeutic potential of psychedelics has grown in recent years. Loosely defined, psychedelics are a class of drugs that induce altered thoughts and sensory perceptions.

The recent wave of new interest has brought two psychedelic compounds to the forefront of the conversation about the use of psychedelic drugs for the treatment of depression and anxiety: ketamine and MDMA.

While these two psychedelic therapy drugs share some similarities, they’re actually quite different in many significant ways. Here, we’ll take a look at these two psychedelics in greater depth, looking closely at their differences and exploring their efficacy as therapeutic alternatives to antidepressants, including discussing ketamine vs MDMA for PTSD and more.

What Is Ketamine?

Before we dive into the ins and outs of this therapeutic alternative to antidepressants and get the ketamine vs MDMA dialogue started, it is important to take a quick look at the history of ketamine. Firstly, ketamine is a drug with a long-standing history in clinical practice.

It was first created over 50 years ago and introduced into clinical practice in the 1960s as a shorter-acting analog of phencyclidine. The first published study about ketamine came out in 1966. This study explored its efficacy as a dissociative anesthetic.

The published findings from the first clinical trials confirmed its profound anesthetic effects. According to the study, ketamine could rapidly produce analgesia and altered state of consciousness with a limited duration of effect, making it safe for repeated administration.

It was first approved by the Food and Drug Administration (FDA) for human use in 1970. The newly FDA-approved drug proceeded to make waves in the clinical setting for decades to come, as it was one of the first anesthetics to provide adequate sedation without compromising respiratory function.

How Is Ketamine Classified?

When it comes to discussing ketamine vs MDMA, it’s important to understand ketamine’s classification. Ketamine is often grouped with psychedelics. While this drug does have dissociative and hallucinogenic properties that make it similar to many other psychedelics, it has some unique distinctions.

First, ketamine differs from traditional psychedelics because of its legal status. While many hallucinogens are pending approval for breakthrough therapy, ketamine has been legal for medical and therapeutic use for over half a century.

Another key difference between ketamine and other psychedelics is the way it works. Other psychedelics tend to override the parts of your brain involved in developing thoughts, while ketamine works by relaxing neurotransmitters rather than overpowering them.

As far as legal classification goes, ketamine is considered a Schedule III drug, maintaining its FDA approval for use as a dissociative anesthetic. This status also allows it to be prescribed off-label for therapeutic use.

Therapeutic Benefits

MDMA and ketamine both have their own therapeutic benefits that we’ll go over. The potential therapeutic benefits of ketamine are well-documented. One of the biggest therapeutic benefits of using ketamine includes its use as a therapeutic alternative for treatment-resistant depression. Up to 30% of people diagnosed with depression see little to no improvement with traditional antidepressants.

Antidepressant effects on the brain typically include both inhibitory and modulatory effects on neurotransmitters, specifically targeting serotonin receptors. These can come with certain drawbacks over time.

Ketamine works differently — it is fast-acting, working within 24 hours of the first dose.

Ketamine is considered an NMDA antagonist. In short, ketamine blocks NMDA glutamate receptors, causing a glutamate surge.

It also helps activate your brain’s AMPA receptors, which are responsible for fast excitatory synaptic transmissions. Together, these can contribute to brain-derived neurotrophic factors, which are important for neuronal survival, healing, growth, and plasticity.

In addition, studies have shown ketamine’s efficacy as an effective treatment for reducing symptoms of depression, anxiety, and post-traumatic stress disorder (PTSD). Ketamine treatments include infusions, nasal sprays (esketamine or Spravato®), and oral ketamine as a sublingual tablet that dissolves under your tongue.

Side Effects

Understanding MDMA vs ketamine means understanding each of their side effects, too. Although it is considered safe for most people, ketamine does have some short-term side effects to be aware of. Physical side effects can include short-term headaches and increased blood pressure, slight dizziness, and nausea. Other dissociative effects include decreased focus and impairment, as well as perceptual disturbances (hallucinations).

What Is MDMA?

When it comes to comparing ketamine and MDMA, understanding their similarities as well as their differences is crucial. Within the scientific and clinical community, MDMA is known as 3,4-methylenedioxymethamphetamine. To consumers, MDMA may be known as “molly” or “ecstasy.” This psychedelic drug, along with others like psilocybin (magic mushrooms) and lysergic acid diethylamide (LSD), has gained increasing attention as a potential therapeutics in mental healing.

The reason for MDMA’s advancement lies in the efforts of MAPS — the Multidisciplinary Association for Psychedelic Studies. More specifically, research has focused primarily on MDMA-assisted therapy for PTSD. Currently, this MDMA-assisted psychotherapy has moved to Phase 3 clinical trials after its recent FDA “breakthrough therapy” designation.

MDMA was first synthesized in 1912 and was used therapeutically (under a clinician’s or therapist’s supervision) from the mid-1970s through the 1980s. While classified as a psychedelic therapy medicine, MDMA could better be described as an empathogen since its benefits focus more on emotions and feelings rather than the standard “mystical experience” of other psychedelics.

MDMA therapeutic research has focused primarily on its potential use for PTSD, autism spectrum disorder, obesity, and ADHD.

Therapeutic Benefits

While ketamine and MDMA are similar in ways, their therapeutic benefits can differ for individuals. Currently, MDMA’s most notable therapeutic benefits are related to its use for treating PTSD. Phase 3 studies found that MDMA, when paired with therapy sessions, significantly lowered PTSD diagnosis among 67% of participants, as compared to 32% of the placebo group. It also appears to be effective at helping those with dissociative forms of PTSD. In this way, we can see that using ketamine vs MDMA for PTSD both have their benefits.

MDMA works by targeting the serotonin system, specifically activating these pathways while inhibiting the reuptake of serotonin.  By increasing serotonin levels in the system, MDMA may cause increases in energy, increases in empathy towards yourself and others, mood elevation and reduced anxiety, and altered sensory experiences.

When MDMA is combined with psychotherapy, it may allow patients to revisit past experiences, traumas, and memories with more compassion and openness.

Side Effects

Of course, when analyzing MDMA vs ketamine, it’s important to note any potential side effects. The side effects of MDMA can include dehydration, hyperthermia (increased body temperature), loss of appetite, erectile dysfunction, increased heart rate and blood pressure, and increased wakefulness. In some cases, auditory or visual hallucinations are possible.

Which Is Better, Ketamine or MDMA?

First, it is important to recognize that ketamine and MDMA are completely different drugs. Each works in different ways. MDMA is known for increased serotonin and oxytocin, whereas ketamine’s dissociative effects are caused by its interactions with glutamate.

They’re also taken in different ways. For example, ketamine can be administered via IM injection, IV infusion, intranasally, and orally. MDMA can only be consumed orally at this time in its clinical development. So, when it comes down to choosing ketamine vs MDMA, what’s your best bet?

As seen above, both medicines offer mental health benefits. However, MDMA’s research has focused on its efficacy in treating PTSD alone. While the research is promising, ketamine offers that and more. In addition to helping those with PTSD, ketamine has also been studied and proven to help those with treatment-resistant depression, anxiety, and bipolar disorder.

At the end of the day, the best treatment for you depends on your mental health conditions, whether you’re choosing between ketamine and MDMA or another form of treatment. Ketamine’s therapeutic effects are more comprehensive at this time, as compared to MDMA. Also, MDMA, while showing promising results, is still in clinical trials.

Another thing about ketamine that makes it stand out involves preparation and integration. When it comes to ketamine therapy, preparation and integration are vital components that make the treatment effective.

Preparation includes the process of setting the intentions for the experience by establishing both the “set” and the “setting.” Set refers to mental preparation while setting includes the preparation of the environment where treatment occurs.

Integration comes after. It includes the process of reflecting and talking about all the feelings and insights that arose during the experience. It is an integral part of the mental healing process to cement the changes that occur.

Who Can Benefit From Ketamine Therapy?

Many people can stand to benefit from ketamine treatment, including those with mood disorders and mental health conditions. At Nue Life, our programs include participation in integration group sessions led by an Integration Specialist. Clients have the opportunity to share their experiences and learn from others’ experiences.

The Bottom Line

Ketamine and MDMA are two psychedelic medicines making a splash as therapeutic alternatives to certain mental health conditions. While each has its benefits, ketamine holds the upper hand when it comes to relief for treatment-resistant depression, anxiety and PTSD.

You can get started by scheduling your free evaluation today. From there, we’ll discuss how our programs work and help answer any questions you have about ketamine treatments.

Treatment at Nue Life

Nue Life believes in holistic treatment, which means that what happens before and after your ketamine experience is equally as important as the experience itself. We want to ensure you have meaningful takeaways from your experiences and help you establish positive new neural pathways.

That’s why we provide one-on-one health coaching and integration group sessions with each of our programs. We’re here to help map out the mind and body connections in your brain and help you discover the insights that lead to true healing.


Ketamine: 50 Years of Modulating the Mind | PMC

Treatment-resistant depression: therapeutic trends, challenges, and future directions | PMC

Ketamine: NMDA Receptors and Beyond | NIH

Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain | PMC

Study Shows How Ketamine Reverses Depression—and How its Benefits Could Be Extended | Newsroom | Weill Cornell Medicine

Research: MDMA-Assisted Therapy for PTSD – Multidisciplinary Association for Psychedelic Studies | MAPS

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study | Nature Medicine

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